Synthesis of structurally unique natural products having glutamate receptor agonist and antagonist activities

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13470471
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Nagasaki University
• Principal Investigator: HATAKEYAMA Susumi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20143000)
• Co-Investigator(Kenkyū-buntansha): IWABUCHI Yoshiharu Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20211766)
• Project Period (FY): 2001 – 2002
• Keywords: dysiherbeine / kaitocephalin / glutamate receptor agonist / glutamate receptor antagonist / amino acid / total synthesis

Research Abstract

The compounds that interact with glutamate receptors are in high demand in order to investigate the relationship between glutamate receptors and brain diseases. These compounds are also useful for designing a new type of glutamate receptor antagonist which may have therapeutic value as a neuroprotective agent. In this research, we focused on dysiherbaine, a glutamate receptor agonist isolated from Dysidea herbacea, and kaitocephalin, a glutamate receptor antagonist isolated from Eupenicillium shearii PF1191 strain, and aimed to develop efficient methods for the syntheses of these compounds.
For dysiherbaine, we have developed an efficient method for the preparation of the key intermediate starting with D-glucose based on highly stereoselective Hosomi-Sakurai reaction to attach the side chain to the pyrane ring and palladium catalyzed cross-coupling reaction of the functionalized enol triflate and the organozinc reagent derived from L-iodoalanine to install the glutamic acid moiety.
For kaitocephalin, we examined 1, 3-butadienylation of the Garner aldehyde derived from L-serine. When the Garner aldehyde was reacted with 2, 3-butadienyltrichlorostannane, prepared in site from 1, 3-butadien-2-yltributylstananne and SnCl_4, the addition reaction proceeded with perfect anti-selectivity to give the compound convertible to kaitocephalin.